Risdiplam in adult non-sitter patients with 5q spinal muscular atrophy: a non-interventional, single centre, observational cohort study

Objective To describe the safety and efficacy of risdiplam in non-sitter adult patients with 5q spinal muscular atrophy (SMA). Methods Type 2 SMA adult patients, who were not eligible for nusinersen, were offered risdiplam through the expanded access program. Patients were followed up with a battery of scales and clinical measures. Results Six non-sitter patients (17 – 46 years old) were treated with risdiplam. One patient reported mild adverse events (dyspepsia and headache). After one year of treatment, all patients showed clinically meaningful improvements in at least one scale and none of them showed any clinically meaningful deterioration. Two patients showed a clinically significant increase in the body mass index and other two in the revised upper limb module. Moreover, clinically meaningful improvements were found in motor (axial and upper limbs), bulbar (speech and swallowing) and respiratory (coughing) domains of functional scales, in five patients. Four subjects achieved at least one of the goals set with the goal attainment scale (GAS). Discussion This series suggests the safety and efficacy of risdiplam in non-sitter adult SMA patients. In these patients, functional scales and GAS are more appropriate than motor scales to detect changes, because they include axial, bulbar and respiratory domains. ### Competing Interest Statement Dr. Vazquez-Costa is funded by grants of the Instituto de Salud Carlos III (JR19/00030, PI Vazquez), served on advisory boards for Biogen and Roche and received travel and speaker honoraria from Biogen and Roche. Dr. Pitarch-Castellano served on advisory boards for Avexis and Biogen and received travel and speaker honoraria from Biogen and Roche; principal investigator for ongoing Biogen clinical trial. ### Clinical Trial NCT04256265 ### Funding Statement This study has received funding from CUIDAME (PIC188-18) and from Instituto de Salud Carlos III (JR19/00030 PI JFVC). The Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER) is initiative from the ISCIII. TS and JFVC are members of the European Reference Network for Rare Neuromuscular Diseases (ERN EURO-NMD). Sponsors did not participate in the study design, data acquisition and analysis, data interpretation or in writing the article ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All patients signed informed consent before the start of risdiplam, and for the publication of this report. Data collection and processing were approved by the Ethics Committee for Biomedical Research of the La Fe Hospital (Valencia). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes JFVC and NCNG had full access to the database population used to create the study population. All data supporting our findings are available on reasonable request.